Introduction: [I-121]I-PK11195 is a high-affinity single photon emission computed tomography radiotracer for peripheral benzodiazepine receptors that has previously been used to measure activated microglia and to assess neuroinflammation in the living human brain. This Study investigates the radiosynthesis of [I-123]I-PK11195 in order to develop a rapid and efficient method that obtains [I-123]I-PK11195 with a high specific activity for in vivo animal and human imaging studies. Methods: The synthesis of [I-123]I-PK11195 was evaluated using a solid-state interhalogen exchange method and an electrophilic iododestannylation method, where bromine and trimethylstannyl derivatives were used as precursors, respectively. In the electrophilic iododestannylation method, the oxidants peracetic acid and chloramine-T were both investigated. Results: Electrophilic iododestannylation produced [I-123]]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than achievable using the halogen exchange method investigated. Using chloramine-T as oxidant provided a rapid and efficient method of choice for the synthesis of [I-123]I-PK11195. Conclusions: [I-123]I-PK11195 has been successfully synthesized via a rapid and efficient electrophilic iododestannylation method, producing [I-123]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than previously achieved. (C) 2008 Elsevier Inc. All rights reserved.